1. Field of the Invention
The invention relates to the methods and apparatus for controlling fluid flow in microfluidic systems. In, particular, the invention provides microvalves for controlling fluid flow from microreservoirs into transfer channels using capillary valving mechanisms. The capillary valving mechanisms of the invention are based on changes in cross-sectional area and geometry of orifices, reservoirs and microchannels and surface treatment of reservoirs and channels. Specific embodiments of the microvalves of the invention are provided to control fluid flow in microchip-based chemical Microsystems using pumping means and in centrifugal rotors and microplatforms as disclosed, for example in International Application WO97/21090. This invention provides microvalving means for use in apparatus useful for performing microanalytic and microsynthetic analyses and procedures, such as microminiaturization of genetic, biochemical and chemical processes related to analysis, synthesis and purification of biological, chemical, environmental and other compounds.
2. Summary of the Related Art
In the field of medical, biological and chemical assays, mechanical and automated fluid handling systems and instruments are known in the prior art.
U.S. Pat. No. 4,279,862, issued Jul. 21, 1981 to Bertaudiere et al. disclose a centrifugal photometric analyzer.
U.S. Pat. No. 4,381,291, issued Apr. 26, 1983 to Ekins teach analytic measurement of free ligands.
U.S. Pat. No. 4,515,889, issued May 7, 1985 to Klose et al. teach automated mixing and incubating reagents to perform analytical determinations.
U.S. Pat. No. 4,676,952, issued Jun. 30, 1987 to Edelmann et al. teach a photometric analysis apparatus.
U.S. Pat. No. 4,745,072, issued May 17, 1998 to Ekins discloses immunoassay in biological fluids.
U.S. Pat. No. 5,061,381, issued Oct. 29, 1991 to Burd discloses a centrifugal rotor for performing blood analyses.
U.S. Pat. No. 5,122,284, issued Jun. 16, 1992 to Braynin et al. discloses a centrifugal rotor comprising a plurality of peripheral cuvettes.
U.S. Pat. No. 5,160,702, issued Nov. 3, 1993 to Kopf-Sill and Zuk discloses rotational frequency-dependent "valves" using capillary forces and siphons, dependent on "wettability" of liquids used to prime said siphon.
U.S. Pat. No. 5,171,695, issued Dec. 15, 1992 to Ekins discloses determination of analyte concentration using two labeling markers.
U.S. Pat. No. 5,173,193, issued Dec. 22, 1992 to Schembri discloses a centrifugal rotor for delivering a metered amount of a fluid to a receiving chamber on the rotor.
U.S. Pat. No. 5,242,803, issued Sep. 7, 1993 to Burtis et al. disclose a rotor assembly for carrying out an assay.
U.S. Pat. No. 5,409,665, issued Apr. 25, 1995 to Burd discloses a cuvette filling in a centrifuge rotor.
U.S. Pat. No. 5,413,009, issued Jul. 11, 1995 to Ekins discloses a method for analyzing analytes in a liquid.
U.S. Pat. No. 5,472,603, issued Dec. 5, 1995 to Schembri discloses an analytical rotor comprising a capillary passage having an exit duct wherein capillary forces prevent fluid flow at a given rotational speed and permit flow at a higher rotational speed.
Anderson, 1968, Anal. Biochem. 28: 545-562 teach a multiple cuvette rotor for cell fractionation.
Renoe et al., 1974 Clin. Chem. 20: 955-960 teach a "minidisc" module for a centrifugal analyzer.
Burtis et al., 1975, Clin. Chem. 20: 932-941 teach a method for a dynamic introduction of liquids into a centrifugal analyzer.
Fritsche et al., 1975, Clin. Biochem. 8: 240-246 teach enzymatic analysis of blood sugar levels using a centrifugal analyzer.
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Cho et al., 1982, Clin. Chem. 28: 1956-1961 teach a multichannel electrochemical centrifugal analyzer.
Bertrand et al., 1982, Clinica Chimica Acta 119: 275-284 teach automated determination of serum 5'-nucleotidase using a centrifugal analyzer.
Schembri et al., 1992, Clin Chem. 38: 1665-1670 teach a portable whole blood analyzer.
Walters et al., 1995, Basic Medical Laboratory Technologies, 3rd ed., Delmar Publishers: Boston teach a variety of automated medical laboratory analytic techniques.
Recently, microannlytical devices for performing select reaction pathways have been developed.
U.S. Pat. No. 5,006,749, issued Apr. 9, 1991 to White disclose methods apparatus for using ultrasonic energy to move microminiature elements.
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International Application, Publication No. WO93/22053, published Nov. 11, 1993 to University of Pennsylvania disclose microfabricated detection structures.
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One drawback in the prior art microanalytical methods and apparati has been the difficulty in designing systems for moving fluids on microchips through channels and reservoirs having diameters in the 10-100 .mu.m range. Microfluidic systems require precise and accurate control of fluid flow and valving to control chemical reactions and analyte detection. Conventional pumping and valving mechanisms have been difficult to incorporate into microscale structures due to inherent conflicts-of-scale. These conflicts of scale arise in part due to the fact that molecular interactions arising out of mechanical components of such valves, which are negligible in large (macroscopic) scale devices, become very significant for devices built on a microscopic scale.
One such phenomenon associated with microscale devices is termed "stiction". Stiction is functionally defined as the adhesion of two components under static conditions. Stiction may be due to a variety of causes, such as electrostatic charge transfer, chemical or hydrogen bonding or precipitation of adherent chemicals while the parts are in contact. In order to overcome stiction, a disproportionately large amount of mechanical or electrical energy must be applied. However, the application of such energy and the accompanying force on the microvalve can completely overwhelm the delicate structural and electrical features of the devices. In addition, the manufacture of complex valves and associated circuitry is challenging and results in prohibitively high manufacturing costs.
Systems that use centripetal force to effect fluid movement in microstructures address the need for a pumping mechanism to effect fluid flow, but do not solve these valving needs. The present invention permits precise and accurate control of valving, flow and metering of fluids in microstructural platforms, including both microchip-based and centrifugal microplatform-based technologies, using structures that take advantage of surface tension and capillarity.